This invention relates to the use of novel steroid compounds, particularly to the use of compounds of the class of etianic acids, for inhibition of blood vessel formation. Certain etianic acids and esters derived therefrom can inhibit blood vessel formation, and can be used in treating solid tumor growth, ophthalmic retinopathies including diabetic, and granulomatous disease, and as a contraceptive, as well.
"Angiogenesis" is the term used to describe new blood vessel formation. Angiogenesis is a feature of many diseases and physiological conditions, for example, ophthalmic retinopathies, granulomatous disease, and solid tumor growth, as well as wound healing and corpus luteum formation. Folkman discusses angiogenesis in a general way in Ann. N.Y. Acad. Sci. 1982, p. 212.
Conditions characterized by angiogenesis may be treated by inhibiting angiogenesis, if the treatment has few side effects. For example, angiogenesis accompanies most solid tumor growth. The prevention of further angiogenesis can inhibit further tumor growth in some cases. As another example, preventing angiogenesis is an effective means of contraception in mammals.
Folkman has demonstrated both that angiogenesis is necessary for tumor growth, and that tumor growth stops if angiogenesis is inhibited. See Science, 221, Aug. 1983, p. 719-725. He reported that if angiogenesis was inhibited by a combination of heparin, or heparin fragments, and cortisone, tumor growth could be stopped and even reversed. He always administered both heparin and a glucocorticoid steroid to achieve the anti-angiogenic effect. One disadvantage that he has recognized is that not all heparins give identical results. (See Science 221 at p. 722) And, in one case, the heparin that gave the best anti-angiogenic activity was removed from the market during the pendancy of the study. Later, he reported the successful use of hydrocortisone and heparin to inhibit angiogenesis in The Third International Symposium on the Biology of Vascular Endothelial Cell, at Cambridge, Mass. June 25-29, 1984.
It would be advantageous to find a class of steroid compounds that are anti-angiogenic, that do not have any other biological effects, particularly severe glucocorticoid effects. The applicant has found that etianic acids and their esters do show anti-angiogenic effects.